Dataset Information

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.

ABSTRACT: PURPOSE:Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS:The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA). RESULTS:The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other. CONCLUSIONS:Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.

SUBMITTER: Fodor LE

PROVIDER: S-EPMC5352576 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.

Fodor Lili E LE Gézsi András A Ungvári Ldikó L Semsei Agnes F AF Gál Zsófia Z Nagy Adrienne A Gálffy Gabriella G Tamási Lilla L Kiss András A Antal Péter P Szalai Csaba C

Allergy, asthma & immunology research 20170501 3

<h4>Purpose</h4>Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes.<h4>Methods</h4>The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control s ...[more]

PMID: 28293931

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Project description:Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. The discovery, stage I cohort involved 306 patients with moderate and severe allergic rhinitis, the stage II study consisted of four cohorts, namely, adult and pediatric asthmatics and corresponding controls. Altogether, there were 1,258 unrelated individuals in these cohorts, out of which 63.9% were children and 36.1% were adults. In stage I, 112 SNPs were screened in the TEK gene of the patients in order to search for associations with asthma and allergic conjunctivitis. The top associated SNPs were selected for association studies on the replication cohorts. The rs3824410 SNP was nominally associated with a reduced risk of asthma in the stage I cohort and with severe asthma within the asthmatic population (p=0.009; OR=0.48) in the replication cohort. In the stage I study, 5 SNPs were selected in conjunctivitis. Due to the low number of adult patients with conjunctivitis, only children were involved in stage II. Within the asthmatic children, the rs622232 SNP was associated with conjunctivitis in boys in the dominant model (p=0.004; OR=4.76), while the rs7034505 showed association to conjunctivitis in girls (p=0.012; OR=2.42). In the lung of a mouse model of asthma, expression changes of 10 Tie2 pathway-related genes were evaluated at three points in time. Eighty percent of the selected genes showed significant changes in their expressions at least at one time point during the process, leading from sensitization to allergic airway inflammation. The expressions of both the Tek gene and its ligands showed a reduced level at all time points. In conclusion, our results provide additional proof that the Tie2 pathway, the TEK gene and its variations might have a role in asthma and allergic conjunctivitis. The gene and its associated pathways can be potential therapeutic targets in both diseases.

Dataset Information

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.

Publications

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.

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